Common infection might set stage for lupus

Infection is known to trigger certain autoimmune diseases, e.g., rheumatic fever and ankylosing spondylitis. The initial immune response against the pathogen is thought to also recognize "self" proteins called autoantigens and may later spread to recognize additional autoantigens. These investigators wished to test their suspicion that Epstein Barr virus (EBV) triggers systemic lupus erythematosus (SLE). They previously showed that the first SLE autoantigen is the RNA-binding protein Ro. Here, they analyzed blood samples from a repository drawn from more than 5 million people. They found 29 people who later developed lupus and who had donated a blood sample before they developed Ro-specific autoantibodies. Nine of these early sera contained autoantibodies that recognized only a single small portion of Ro. All of these early, Ro-specific antibodies cross-reacted with a completely different small fragment of the EBV nuclear protein EBNA-1, suggesting that the crossreaction could be an early event in the disease. To test this, they immunized rabbits with peptides matching Ro or EBNA-1. Strikingly, both groups of rabbits developed lupus-like symptoms, including reduced numbers of white blood cells (leukopenia), clotting factors (thrombocytopenia) and kidney function. This paper connects a common infection with lupus. It remains to be determined why lupus develops in relatively few of the many EBV infected adults.
McClain et al. Nat.Med. 11, 85 - 89 (2004) "Early events in lupus humoral autoimmunity suggest initiation through molecular mimicry"